Yamaguchi K, Nagai S, Ninomiya-Tsuji J, Nishita M, Tamai K, Irie K, Ueno N, Nishida E, Shibuya H, Matsumoto K
Department of Molecular Biology, Graduate School of Science, Nagoya University, Nagoya, Japan.
EMBO J. 1999 Jan 4;18(1):179-87. doi: 10.1093/emboj/18.1.179.
Signals elicited by transforming growth factor-beta (TGF-beta) superfamily ligands are generated following the formation of heteromeric receptor complexes consisting of type I and type II receptors. TAK1, a member of the MAP kinase kinase kinase family, and its activator, TAB1, participate in the bone morphogenetic protein (BMP) signaling pathway involved in mesoderm induction and patterning in early Xenopus embryos. However, the events leading from receptor activation to TAK1 activation remain to be identified. A yeast interaction screen was used to search for proteins that function in the pathway linking the receptors and TAB1-TAK1. The human X-chromosome-linked inhibitor of apoptosis protein (XIAP) was isolated as a TAB1-binding protein. XIAP associated not only with TAB1 but also with the BMP receptors in mammalian cells. Injection of XIAP mRNA into dorsal blastomeres enhanced the ventralization of Xenopus embryos in a TAB1-TAK1-dependent manner. Furthermore, a truncated form of XIAP lacking the TAB1-binding domain partially blocked the expression of ventral mesodermal marker genes induced by a constitutively active BMP type I receptor. These results suggest that XIAP participates in the BMP signaling pathway as a positive regulator linking the BMP receptors and TAB1-TAK1.
转化生长因子-β（TGF-β）超家族配体引发的信号是在由I型和II型受体组成的异源二聚体受体复合物形成后产生的。TAK1是丝裂原活化蛋白激酶激酶激酶家族的成员，其激活剂TAB1参与非洲爪蟾早期胚胎中胚层诱导和模式形成所涉及的骨形态发生蛋白（BMP）信号通路。然而，从受体激活到TAK1激活的具体事件仍有待确定。利用酵母相互作用筛选来寻找在连接受体与TAB1-TAK1的信号通路中发挥作用的蛋白质。人类X染色体连锁凋亡抑制蛋白（XIAP）被分离为一种TAB1结合蛋白。XIAP不仅在哺乳动物细胞中与TAB1相关，还与BMP受体相关。将XIAP mRNA注射到背侧卵裂球中，以TAB1-TAK1依赖的方式增强了非洲爪蟾胚胎的腹侧化。此外，一种缺少TAB1结合结构域的截短形式的XIAP部分阻断了由组成型活性BMP I型受体诱导的腹侧中胚层标记基因的表达。这些结果表明，XIAP作为连接BMP受体与TAB1-TAK1的正向调节因子参与BMP信号通路。
